Self-assembly in forming molecularly defined, high-ordered structures largely relies on non-covalent interactions. Structures formed from self-assembly are capable of entrapping molecules in solution during the assembly process, resulting in injectable carriers suitable for delivery of hydrophobic and hydrophilic agents.
However, self-assembled structures are generally unstable and are subject to biological, chemical, and mechanical perturbations. For example, the interactions of self-assembled structures with blood proteins are diverse and complex, often leading to dramatic effects on the stability and in vivo behavior of assembled structures. Serum lipoproteins may destabilize the amphiphilic building blocks of assembled structures by perturbing their hydrophobic-hydrophilic interactions. Irregularities at phase boundaries in the assembled structures may promote the destabilizing effects. (Bonte F and Juliano R L, Chemistry and Physics of Lipids, 40:359-372 (1986)). The disruption of assembled structures often leads to loss of contents and failure of therapeutic delivery.
Controlled release in response to pathological environments presents a significant challenge with self-assembled structures. The ability of drug delivery systems to reach target tissues from the point of administration can be limited by multiple barriers. For example, orally administered drug delivery systems must pass through the acid in the stomach, be absorbed across the intestinal epithelium, and avoid hepatic clearance and nonspecific uptake. Systemically administered, self-assembled materials are challenged with destabilization with blood proteins, loss of cargo, and rapid clearance from circulation.
Therefore, it is an object of the present invention to provide stabilized, self-assembled hydrogel or organo-gel formed with generally regarded as safe materials. It is another object of the present invention to provide stabilized self-assembled carriers for controlled release in response to biological stimuli.
It is yet another object of the present invention to provide a method of delivering active agents to disease sites with increased dosing efficacy and lower toxicity.